A significant body of evidence has accumulated demonstrating that arterial glycosaminoglycans are involved in atherosclerosis, but few investigators have examined these carbohydrates as they exist in situ as proteoglycans. The purpose of this study is to obtain information on proteoglycans from normal and atherosclerotic human and pigeon aortas to test the hypothesis that compositional and/or conformational changes in arterial proteoglycan aggregates are initiating factors or result in the acceleration of atherosclerosis. The studies involve dissociative extraction, purification and characterization of proteoglycan populations including chemical and structural examination of proteoglycan aggregates, monomers, glycosaminoglycans, core proteins and aggregate-stabilizing link proteins. We plan to use two model systems to examine proteoglycan modifications influenced by genotype and by altered cellular environment. One system will be normal and atherosclerotic arteries of nondiabetic and diabetic patients to provide normal structure and composition, the influence of atherosclerosis and the influence of diabetes mellitus on proteoglycans. The second system will be a genetic strain of White Carneau pigeon (WC-2) that develops more severe atherosclerosis in the absence of hypercholesterolemia and other atherosclerosis risk factors. We plan to demonstrate an influence of genotype on proteoglycans by studying aortas from WC-2 embryos. Through studies designed to examine the effects of age, naturally occurring atherosclerosis and diet-exacerbated atherosclerosis, we will attempt to assess genotype-environment interaction and the role of aortic proteoglycans in atherosclerosis of the WC-2 pigeon. The studies test the hypothesis that genotype and factors modifying genotypic expression result in the production of proteoglycan aggregates of smaller mean size or altered composition. Ultimately the research could provide a further understanding of the initiation and progression of the atherosclerotic plaque.